Passive and wireless, implantable glucose sensing with phenylboronic acid hydrogel-interlayer RF resonators

Abstract

A phenylboronic acid-based, hydrogel-interlayer Radio-Frequency (RF) resonator is demonstrated as a highly-responsive, passive and wireless sensor for glucose monitoring. Constructs are composed of unanchored, capacitively-coupled split rings interceded by glucose-responsive hydrogels. Phenylboronic acid-hydrogels exhibit volumetric and dielectric variations in response to environmental glucose concentrations—these are efficiently converted to large shifts in the resonant response of interlayer-RF sensors. These tiny, stretchable and scalable sensors (5 mm × 5 mm x 250 μm) require no microelectronics or power at the sensing node and can be read-out remotely via near-field coupling. Sensors exhibit high sensitivities (~10% shift in resonant frequency—corresponding to 50 MHz—per 150 mg/dL of glucose), possess a limit of detection of 10 mg/dL, and a step response time of approximately 1 h to abrupt shifts in carbohydrate concentration. Notably, these sensors exhibited no signal drift or hysteresis over the time periods characterized herein (45 days at room temperature). We transform sensors into bioelectronic RF reporter-tags via the attachment of a single LED—these remotely report on glucose concentration via emitted light. We anticipate the non-degradative, long-term nature of both RF read-out and phenylboronic acid-based hydrogels will enable biosensors capable of long-term, remote read-out of glucose.